What question did this study set out to answer?

The research aims to explore the relationship between childhood-onset dystonia and specific genetic findings in the VPS13C gene.

April 22, 2026

Childhood‐Onset Dystonia and Biallelic Findings in VPS13C : An Exploratory Report

Key Points

The research aims to explore the relationship between childhood-onset dystonia and specific genetic findings in the VPS13C gene.
Identified and classified VPS13C variants using ACMG/AMP guidelines.
Utilized in silico prediction algorithms to evaluate the pathogenicity of the variants.
Analyzed the zygosity and minor allele frequency of variants from gnomAD.
Two VPS13C missense variants were identified as variants of uncertain significance (VUS).
In silico tools predicted deleterious effects for both variants.
The classification was supported by specific ACMG criteria (PM2_supporting and PP3).

Abstract

Ethical Compliance Statement: The authors confirm that approval of an institutional review board was not required for this work. Informed written consent for publication was obtained from the patient's parent. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Funding Sources and Conflicts of Interest: No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work. Financial Disclosures for the Previous 12 Months: All authors have no financial disclosures or conflicts of interest related to the manuscript. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. TABLE S1. Genetic annotation and ACMG/AMP-based classification of VPS13C variants identified in the proband. This table summarizes the genomic and computational characteristics of the two VPS13C missense variants, including zygosity, minor allele frequency (MAF) from the Genome Aggregation Database (gnomAD), in silico pathogenicity predictions, and database annotations (ClinVar/dbSNP). In silico prediction scores represent the number of algorithms (eg, SIFT, PolyPhen-2, MutationTaster, and CADD) predicting a deleterious effect. Variant classification was performed according to the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines. Both variants were classified as variants of uncertain significance (VUS), supported by PM2ₛupporting and PP3 criteria. AA, amino acid; Het, heterozygous; MAF, minor allele frequency (gnomAD) ; TW, Taiwan Biobank; NR, not reported; in silico prediction indicates the number of deleterious predictions among 13 computational tools; ACMG, American College of Medical Genetics and Genomics; VUS, variant of uncertain significance. Data S1. Coidisclosure. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

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Cite This Study

Lee et al. (Sun,) studied this question.

synapsesocial.com/papers/69e8661d6e0dea528ddea8bd https://doi.org/https://doi.org/10.1002/mdc3.70654

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